Malaria, a disease of humans since antiquity, remains man's foremost killer. Since World War II concerted efforts to eradicate this disease have met with limited success largely because of the development of parasite resistance to what were once effective antimalarial drugs. One of the logical approaches to the development and testing of new chemotherapeutic agents, ones that would specifically inhibit parasite growth and reproduction, would be to study the biochemical differences between the malaria parasite and its host, and then to tailor-make compounds that would adversely affect only the parasite. The proposed program of research is designed to study: 1) The mechanisms of purine transport into the erythrocytic and exoerythrocytic stages of the malarial parasite (Plasmodium lophurae) and host cells; 2) The metabolic interconversions of purines, nucleosides and nucleotides that take place during the course of the malaria infection; 3) The optimum conditions for a P. lophurae-derived cell-free protein synthesizing system, and 4) The in vitro effectiveness of antimalarial drugs using the malarial parasite protein synthesizing system. Standard isotope and enzymatic techniques will be employed to follow transport and metabolic pathways; the cell-free protein synthesizing system will use techniques of cell-fractionation, ultracentrifugation and isotope incorporation.